A large body of in vitro evidence has accummulated which suggests that activated macrophages from hosts with chronic infections or which have been treated with immunomodulating substances might play an important role in prevention of tumor development or in resistance to existing tumors. Experiments will be performed to more clearly define the mechanisms underlying the adverse effects that activated macrophages exert on tumors target cells. The relative contributions that macrophage-mediated cytostatic and cytocidal effects have on this overall adverse effect will be studied as will the ability of lymphocytes or their products to bolster (or suppress) the cytotoxic effects of activated macrophages. We will determine the cytotoxic efficacy of macrophages from different anatomical compartments, and we will define the most efficient methods of preferentially activating macrophages from different anatomical compartments. In humans, we will study in vitro peripheral blood monocytes and monocyte-derived macrophages, as well as tissue macrophages from the spleen, to determine their effects on established lines of normal and neoplastic human cell lines. Experiments will be performed to activate these human monocytes and macrophages in vitro to kill tumor cells by cultivating them in the presence of lymphocytes (or lymphocyte products) and mitogens or specific antigen.